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Evaluation of the DAMSUN-HF trial:the role of an artificial intelligence stethoscope in detecting reduced ejection fraction in patients living in a low-resource region
No full textEvaluation of ejection fraction (EF) is paramount for patients with symptoms of heart failure. While transthoracic echocardiography (TTE) is the most common way to evaluate EF, recent advances in artificial intelligence (AI) have opened the door for alternative methods to screen for reduced EF with smaller and more portable technology. The DAMSUN-HF study evaluated the accuracy of an AI-based stethoscope for detecting reduced EF (≤40%) in patients with symptoms of heart failure in a region with geographic and economic barriers to obtaining timely TTE. This mini-review examines the DAMSUN-HF study and highlights the potential clinical implications of the study findings.</p
Sustained diabetes remission induced by FGF1 involves a shift in transcriptionally distinct AgRP neuron subpopulations
No full textIn rodent models of type 2 diabetes, a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) induces sustained remission of hyperglycemia. Overactive agouti-related peptide (AgRP) neurons, located in the hypothalamic arcuate nucleus, are a hallmark of diabetic states, and their long-term inhibition has been linked to FGF1's antidiabetic effects. To investigate the underlying mechanism(s), we performed single-nucleus RNA sequencing of the mediobasal hypothalamus at Days 5 and 14 post-injection in wild-type and diabetic (Lepob/ob) mice treated with FGF1 or vehicle. We found that AgRP neurons from Lepob/ob mice form a transcriptionally distinct, hyperactive subpopulation. By Day 5, icv FGF1 induced a subset of these neurons to shift toward a less active, wild-type-like state, characterized by reduced activity-linked gene expression that persisted through Day 14. Spatial transcriptomics revealed that this FGF1-responsive AgRP subset is positioned dorsally within the arcuate nucleus. The transcriptional shift was accompanied by transcriptional processes indicative of increased GABAergic signaling, axonogenesis, and astrocyte–AgRP and oligodendrocyte–AgRP interactions. These glial inputs involve astrocytic neurexins and the perineuronal net (PNN) component phosphacan, suggesting both intrinsic and extrinsic mechanisms underlie FGF1-induced AgRP silencing. Combined with evidence that FGF1 increases PNN assembly in the arcuate nucleus, our findings reveal a cell-type–specific model for how FGF1 elicits long-term reprogramming of hypothalamic circuits to achieve diabetes remission.</p
PNPLA3 and TM6SF2 exacerbate the impact of alcohol and metabolic dysfunction on liver fibrosis
No full textBackground & Aims: Genetic predisposition (especially variants in PNPLA3 and TM6SF2), metabolic dysfunction, and alcohol consumption are established risk factors for steatotic liver disease (SLD) and progression of fibrosis. However, the clinical relevance of their interaction and its implications for patient management remain unclear. Methods: We cross-sectionally analyzed data from two cohorts: patients referred to tertiary liver care (N = 1,554) and individuals at risk for SLD (N = 1,728). Multivariable regression models with and without interaction terms were used to assess the independent and interactive effects of genetic risk variants, metabolic dysfunction (HOMA-IR, BMI), and alcohol intake on liver fibrosis severity as assessed by liver stiffness measurement (LSM). Results: Mean age was 52 and 56 years in the Tertiary-care cohort and the At-risk cohort, respectively. Most participants were male, 23% and 53% suffered from obesity, and 39% and 58% were categorized as insulin resistant, respectively. Median LSM was 5.5 kPa and 4.7 kPa, with 21% and 9.6% having LSM ≥8 kPa, respectively. In total, 48% and 44% carried at least one PNPLA3 G-allele (C/G or G/G), and 18% and 15% the TM6SF2 T-allele (C/T or T/T), respectively. In multivariable regression without interaction terms, LSM was associated with HOMA-IR, alcohol consumption, BMI (At-risk cohort), PNPLA3 and TM6SF2. However, when allowing for interactions, the independent effects of genetic risk variants disappeared. Instead, PNPLA3 potentiated the association of HOMA-IR (p <0.001/p = 0.016) and severe alcohol consumption (p <0.001/p = 0.093) with LSM. TM6SF2 amplified the effect of BMI (p = 0.006) and severe alcohol consumption (p <0.001) on LSM in the Tertiary-care-cohort. Conclusions: Our findings indicate that PNPLA3 and TM6SF2 variants do not act as independent determinants of liver fibrosis once gene–environment interactions are considered. Instead, they amplify the harmful effects of metabolic dysfunction and alcohol consumption in individuals evaluated for SLD, creating a synergistic risk profile. Impact and implications: Our findings indicate that fibrosis progression in steatotic liver disease is mediated by an interaction of environmental risk factors (obesity, insulin resistance, alcohol consumption) and genetic risk variants, such as PNPLA3 and TM6SF2, but not by genetic variants alone. This highlights the importance of acknowledging these gene–environment interactions for patient counselling and risk stratification.</p
Spike antibody levels and risk of SARS-CoV-2 reinfection:a two-year cohort study in previously infected adults
No full textBackgroundThe need for a validated correlate of protection (CoP) for SARS-CoV-2 remains unmet, particularly in immunosuppressed or vulnerable populations. Antibody quantification is widely available, but the relationship with reinfection risk remains uncertain.MethodsWe conducted a two-year cohort study in Denmark including 2960 adults with previous SARS-CoV-2 infection and more than 9000 plasma samples collected between 2020 and 2022. Spike antibody concentrations were measured using the Roche Elecsys® Anti-SARS-CoV-2 S assay. Weekly antibody levels were modelled by nonlinear mixed-effect models and linked to reinfection risk using a competing-risk Cox regression explicitly adjusted for infection pressure and individual testing frequency.FindingsAmong 1600 participants with longitudinal antibody follow-up, 133 reinfections were observed during a median of 22 weeks at risk. Each tenfold (log10) increase in spike antibody level was associated with a 28 % reduction in reinfection hazard (HR 0.72, 95 % CI 0.57–0.90, p = 0.0045). This effect was consistent across multiple sensitivity analyses and robust to fluctuations in infection pressure and testing practices. No discrete antibody threshold was identified, suggesting a continuous, dose-response association between antibody concentration and protection.InterpretationHigher spike antibody levels were consistently associated with lower risk of SARS-CoV-2 reinfection, supporting their use as continuous markers of protection. Although assay-specific and without a single protective cutoff, antibody measurements may help monitor patient groups prone to poor vaccine responses—such as those receiving chemotherapy or immune-modulating drugs—and guide individualized revaccination once immune competence recovers.BACKGROUND: The need for a validated correlate of protection (CoP) for SARS-CoV-2 remains unmet, particularly in immunosuppressed or vulnerable populations. Antibody quantification is widely available, but the relationship with reinfection risk remains uncertain.METHODS: We conducted a two-year cohort study in Denmark including 2960 adults with previous SARS-CoV-2 infection and more than 9000 plasma samples collected between 2020 and 2022. Spike antibody concentrations were measured using the Roche Elecsys® Anti-SARS-CoV-2 S assay. Weekly antibody levels were modelled by nonlinear mixed-effect models and linked to reinfection risk using a competing-risk Cox regression explicitly adjusted for infection pressure and individual testing frequency.FINDINGS: Among 1600 participants with longitudinal antibody follow-up, 133 reinfections were observed during a median of 22 weeks at risk. Each tenfold (log10) increase in spike antibody level was associated with a 28 % reduction in reinfection hazard (HR 0.72, 95 % CI 0.57-0.90, p = 0.0045). This effect was consistent across multiple sensitivity analyses and robust to fluctuations in infection pressure and testing practices. No discrete antibody threshold was identified, suggesting a continuous, dose-response association between antibody concentration and protection.INTERPRETATION: Higher spike antibody levels were consistently associated with lower risk of SARS-CoV-2 reinfection, supporting their use as continuous markers of protection. Although assay-specific and without a single protective cutoff, antibody measurements may help monitor patient groups prone to poor vaccine responses-such as those receiving chemotherapy or immune-modulating drugs-and guide individualized revaccination once immune competence recovers.</p
Type 2 diabetes and age-related cognitive decline over 40 years in Danish men-A cohort study based on the Danish Aging and Cognition (DanACo) cohort
No full textAIM: The extant literature on type 2 diabetes and cognitive decline is based on short cognitive follow-ups and assessments of baseline cognitive ability after diagnosis. The objective was to investigate the influence of type 2 diabetes on cognitive decline over a period of on average 44 years.MATERIALS AND METHODS: This cohort study included 5,147 men from the Danish Aging and Cognition cohort consisting of a late mid-life (mean age 64.2 years) follow-up of men with intelligence test scores (IQ) available from statutory conscription board examinations in young adulthood (mean age 20.4 years). Follow-up included re-administration of the conscription board intelligence test and a comprehensive questionnaire. Exposure was self-reported but register-based type 2 diabetes and duration of disease were also calculated. Cognitive decline was defined as both IQ change (baseline-follow-up) and significant IQ decline based on the reliable change index (cut-off: 13.2 IQ-points). Associations were analyzed in linear and logistic regression models.RESULTS: Men having type 2 diabetes had a 1.81 IQ points (95%CI:1.14,2.49) larger decline compared to men without diabetes when adjusting for baseline IQ, years of education, follow-up age, retest interval, depression, and smoking status. Moreover, type 2 diabetes was associated with 1.42 times higher odds of a significant IQ decline and longer duration was associated with a larger, though not statistically significant, decline. The participation rate was 13.4%, and the participants were healthier and more well-educated than non-participants. To account for potential selection bias, inverse probability weights (IPW) were calculated based on baseline characteristics. The analyses applying these weights yielded similar estimates.CONCLUSION: Type 2 diabetes was associated with modestly greater cognitive decline and higher odds of a statistically significant (>13.2 IQ points) and clinically relevant decline. Finally, the alignment between main and IPW results indicates the findings are robust and likely generalizable.</p
Longitudinal Immune Profiling of T Cell Exhaustion During IL-17A Blockade in a Patient With HLA-B27-negative Spondyloarthritis and Sjögren’s Syndrome:A Case Report
No full textBackground/Aim: Coexisting Sjögren’s syndrome (SS) and human leukocyte antigen-B27 (HLA-B27)-negative ankylosing spondylitis (AS) is rare and therapeutically challenging. In patients with prior Stevens-Johnson syndrome (SJS), non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated and tumor necrosis factor (TNF) inhibitors may be insufficient. Interleukin-17A (IL-17A) blockade with secukinumab offers an alternative, though its long-term effects on T cell exhaustion and regulation remain unclear. This report examines immune exhaustion and regulatory dynamics during IL-17A inhibition in a complex autoimmune case. Case Report: A 52-year-old man with SJS, SS, and HLA-B27-negative AS switched to secukinumab after inadequate TNF inhibition. Flow cytometry over five years (2020, 2023, 2025) tracked early therapy, steroid tapering, and long-term stability. Initial immune profiling revealed expanded effector T cells [Fas cell surface death receptor (Fas)+, programmed death protein 1 (PD-1)+, T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)+] and reduced regulatory subsets. Over time, as disease activity improved, exhaustion markers declined and regulatory T cell (Treg) populations partially recovered. By 2025, the patient maintained low disease activity with minimal steroid exposure. Laboratory data confirmed remission [C-reactive protein (CRP) 0.10 mg/dl, erythrocyte sedimentation rate (ESR) 2 mm/h], while patient-reported indices [Bath ankylosing spondylitis disease activity index (BASDAI) 4.1, ankylosing spondylitis disease activity score using C-reactive protein (ASDAS-CRP) 2.0] reflected stable low-to-moderate disease activity. Naïve T cells continued to show intermittent PD-1 and killer cell lectin-like receptor G1 (KLRG1) expression, suggesting persistent low-level immune adaptation. Conclusion: This case shows phased immune rebalancing under long-term IL-17A blockade. Serial monitoring revealed dynamic exhaustion marker changes and partial regulatory recovery linked to clinical improvement, underscoring the value of longitudinal immune profiling for personalized management of complex autoimmune syndromes.</p
Effect of micronutrients on fertility and aneuploidy rates in human conceptions: a systematic review and meta-analysis
No full textTo make clinical recommendations based on current uncertain evidence, we systematically reviewed and conducted meta-analyses on the influence of micronutrient supplementation on preclinical and clinical reproductive outcomes. PubMed and Scopus were searched until 12.11.2024. Parallel-grouped intervention studies with women undergoing fertility treatment with micronutrient supplementation or micronutrient addition to in vitro maturation media were included. Primary outcomes were oocyte maturation and aneuploidy rates, pregnancy, miscarriage, and live birth rate. Five out of 1,810 studies were included. In three clinical studies, 314 women underwent fertility treatment with coenzyme Q10 (CoQ10) or control treatment. CoQ10 increased oocyte retrieval and live birth rates only for women with diagnosed poor ovarian response (POR) and increased pregnancy rates for women with POR or polycystic ovarian syndrome (PCOS). CoQ10 showed no effect on miscarriages. In two in vitro studies, 127 women donated 241 immature oocytes which matured with CoQ10 or resveratrol. CoQ10 increased oocyte maturation, and decreased oocyte and chromosome aneuploidy rates for women of advanced maternal age (AMA). Resveratrol showed no effect. CoQ10 supplementation improved most preclinical outcomes and pregnancy rates but improved live birth rates only for women with POR. Women of AMA or women with POR or PCOS benefitted more from micronutrient supplementation
Cooperative Squeezing of Internal and Collective Spins in an Atomic Ensemble
No full textCreating highly spin-squeezed states for quantum metrology surpassing the standard quantum limit is a topic of great interest. Spin squeezing has been achieved by either entangling different atoms in an ensemble, or by controlling the multilevel internal spin state of an atom. Here, we experimentally demonstrate combined internal and collective spin squeezing in a hot atomic ensemble with 1011 rubidium atoms. By synergistically combining these two types of squeezing and carefully aligning their squeezing quadratures, we have achieved a metrologically relevant spin squeezing of -6.21 + 0.84 dB, significantly outperforming the results obtained by utilizing either type of squeezing alone in our system. Our approach provides a new perspective on fully harnessing the degrees of freedom inherent in quantum states of an atomic ensemble
Gravitational memory in generalized Proca gravity
No full textWe investigate the gravitational memory effect in the full generalized Proca gravity, the most general metric theory including a gravitational Proca field with derivative self-interactions that still maintains second-order equations of motion. Building on our previous works on memory in other massless and massive metric theories, we extend a unified framework for computing displacement memory and apply it to generalized Proca gravity. We identify two nontrivial, physically distinct classes of background conditions of generalized Proca theory within the assumption of asymptotic flatness: a Lorentz-invariant but massive case, and a Lorentz-violating, massless case. The former exhibits dispersive scalar and vector modes and allows a Horndeski-like treatment of memory, while the latter resembles the asymptotic dynamics of Einstein-AE ther theory, including the same Lorentz-breaking effects on displacement memory. In both cases, we derive the fully gauge-invariant and dynamical second-order action, derive the effective stress-energy tensor, and study its contribution to the memory integral. We highlight the distinction between phase and group velocity in the tensor memory formula sourced by dispersive propagating modes. Finally, we reemphasize how observational constraints on Lorentz violation may be imposed by the structure of the memory signal
Dizziness and impaired postural balance in older patients receiving chemotherapy treatment:A systematic review and meta-analysis
No full textIntroductionDizziness and balance impairments are underexplored symptoms in older adults with cancer. Age-related factors, comorbidities, and chemotherapy may contribute to its prevalence and severity, potentially affecting quality of life, increasing fall risk, and delaying treatment. Data on the incidence and prevalence of these symptoms are limited. This systematic review aimed to summarize the evidence and estimate the incidence and prevalence of dizziness or vertigo and impaired postural balance in patients with cancer ≥65 years receiving chemotherapy.Materials and MethodsWe searched PubMed, EMBASE, CENTRAL, and CINAHL in May 2025 without date or language restrictions. Cross sectional studies, cohort studies, randomized controlled trials, and mixed method studies investigating incidence and/or prevalence of dizziness or vertigo and impaired postural balance were included. Random-effects meta-analysis, employing the inverse-variance method, was applied. Certainty of evidence was rated by the Grading of Recommendations Assessment and Evaluation (GRADE) approach.ResultsFrom 15,614 title/abstracts screened, 14 studies (1259 participants) were included. Incidence could not be evaluated. Studies reporting prevalence across multiple chemotherapy regimens contributed separate estimates for each regimen. Meta-analysis included 25 prevalence estimates for dizziness and three for impaired postural balance. The pooled prevalence of dizziness was 15 % (95 % CI:10 %–22 %). Assessor-reported prevalence using the Common Terminology Criteria for Adverse Events (CTCAE) was 11 % (95 % CI: 8 %–16 %), while patient-reported prevalence rate using the European Organisation for Research and Treatment of Cancer Chemotherapy Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20), or a self-constructed questionnaire was 35 % (95 % CI: 20 %–53 %). Most studies demonstrated a high risk of bias, and certainty of evidence was very low due to unstructured assessor-reported measurement methods. Impaired postural balance prevalence from one study was 48 % (95 % CI: 39 %–57 %) with low certainty of evidence. Prevalence of dizziness and impaired postural balance did not differ significantly across chemotherapy regimens.DiscussionPrevalence of dizziness and impaired postural balance in older patients receiving chemotherapy varied substantially depending on the measurement method, with higher rates in patient-reported outcomes. Certainty of evidence was low primarily due to limitations in outcome measures. Future studies should incorporate patient-reported outcome measures and a systematic objective baseline assessment for a comprehensive evaluation of these symptoms.Trial registration: PROSPERO CRD42024585974.Introduction Dizziness and balance impairments are underexplored symptoms in older adults with cancer. Age-related factors, comorbidities, and chemotherapy may contribute to its prevalence and severity, potentially affecting quality of life, increasing fall risk, and delaying treatment. Data on the incidence and prevalence of these symptoms are limited. This systematic review aimed to summarize the evidence and estimate the incidence and prevalence of dizziness or vertigo and impaired postural balance in patients with cancer ≥65 years receiving chemotherapy. Materials and Methods We searched PubMed, EMBASE, CENTRAL, and CINAHL in May 2025 without date or language restrictions. Cross sectional studies, cohort studies, randomized controlled trials, and mixed method studies investigating incidence and/or prevalence of dizziness or vertigo and impaired postural balance were included. Random-effects meta-analysis, employing the inverse-variance method, was applied. Certainty of evidence was rated by the Grading of Recommendations Assessment and Evaluation (GRADE) approach. Results From 15,614 title/abstracts screened, 14 studies (1259 participants) were included. Incidence could not be evaluated. Studies reporting prevalence across multiple chemotherapy regimens contributed separate estimates for each regimen. Meta-analysis included 25 prevalence estimates for dizziness and three for impaired postural balance. The pooled prevalence of dizziness was 15 % (95 % CI:10 %–22 %). Assessor-reported prevalence using the Common Terminology Criteria for Adverse Events (CTCAE) was 11 % (95 % CI: 8 %–16 %), while patient-reported prevalence rate using the European Organisation for Research and Treatment of Cancer Chemotherapy Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20), or a self-constructed questionnaire was 35 % (95 % CI: 20 %–53 %). Most studies demonstrated a high risk of bias, and certainty of evidence was very low due to unstructured assessor-reported measurement methods. Impaired postural balance prevalence from one study was 48 % (95 % CI: 39 %–57 %) with low certainty of evidence. Prevalence of dizziness and impaired postural balance did not differ significantly across chemotherapy regimens. Discussion Prevalence of dizziness and impaired postural balance in older patients receiving chemotherapy varied substantially depending on the measurement method, with higher rates in patient-reported outcomes. Certainty of evidence was low primarily due to limitations in outcome measures. Future studies should incorporate patient-reported outcome measures and a systematic objective baseline assessment for a comprehensive evaluation of these symptoms. Trial registration: PROSPERO CRD42024585974.</p